This invention relates to a method and devices for the treatment of a biological material with a magnetic field. The invention is useful in the treatment of plants and parts thereof, plant tissue culture, living cells, etc.
Conventional vegetative plant propagation techniques for stimulating root formation in cuttings that are widely used in nurseries and greenhouses typically utilize various chemical materials for treating the cuttings and soil. This technique generally consists of the following. Cuttings that are to undergo the rooting process are taken from a tree. Foliage is removed only from the lower part of each cutting, while the upper part of the cutting remains foliaged. The foliage-free part of the cutting is then dipped into a powder or solution of a suitable hormone substance, such as the synthetic axin xe2x80x9cIndolyl-3-Butric acidxe2x80x9d (IBA), commercially available from Sigma Chemical CO., U.S.A. This chemical material penetrates through a relatively friable end section of the cutting, affecting the growth hormone thereof, and thereby stimulating the root formation. As to the upper, untreated part of the cutting, the foliage produces natural axin which is transferred towards the lower part and also affects the root formation at a further stage, the so-called xe2x80x9cMass Root Formation Treatmentxe2x80x9d. More specifically, treated cuttings are transplanted into special trays filled with soil, where they are further treated over a long period of time on special tables provided with a heating system under the trays and a water sprinkling system.
Techniques of treating biological materials with a magnetic field have been developed, and are disclosed, for example, in the following publications: U.S. Pat. Nos. 4,587,957; 4,757,804; 5,077,934; EP 0459540; EP 0039163; EP 0392626; DE 3613891; RU 2095966; JP 62260240 and G 9102416.
According to some of these techniques, a biological material is subjected to a time-varying magnetic field, e.g., a pulsating magnetic field. However, such a field is typically created by solenoids or coils. The values of the magnetic induction of a magnetic field produced by a solenoid or coil change along one axis (that coincides with the geometrical axis of the solenoid or coil) and reach the amplitude value. Such a magnetic field is characterized by magnetic force lines that intersect the biological material under treatment, and are also oriented along the geometrical axis of the solenoid or coil. It is known that a biological material is characterized by its own microscopic and macroscopic currents occurring within the atoms, molecules, cells, tissues and organs. These currents, in turn, create magnetic fields. In accordance with the known law of electromagnetic induction, the pulsating field produced by a solenoid or coil creates an electromagnetic disturbance and a corresponding response inside the biological material, essentially in a plane perpendicular to the geometrical axis of the solenoid or coil. The disturbance and response vary with the changes in the values of the magnetic induction of the pulsating field.
The techniques directed towards altering the growth of a young tree utilize a strip formed by permanent magnets of alternating polarity mounted stationary around the stem of the tree, or the deposition of a mixture of a ferromagnetic powder on the stem and/or branches.
According to the technique disclosed in DE3613891 aimed at treating seeds, the magnetization of iron in the seeds by an external magnetic field is utilized.
The present invention provides for the manipulation of a biological material with a magnetic field by providing a novel method and device for subjecting a biological material in vitro or in vivo to a coordinate varying magnetic field, to produce a desired physiological effect.
The term xe2x80x9cbiological materialxe2x80x9d refers to material obtained from a biological source, having at least the complexity of a cell. This term refers both to eukaryotic and prokaryotic cells from either plant or animal source, present, for example, in a cell culture; to tissues (from plant or animal) present in a tissue culture, to isolated organs (such as plant stems, plant cuttings, bones, spine, heart, kidney, corneal blood bone marrow); to tissues present inside the organism, as well as to the full organism itself (both full plant and full animal organism).
The manipulation of the biological material may take place in vitro on isolated cells, tissues, or organs; may be carried out ex vivo on cells, or tissues which are manipulated and then returned to the body of the individual; or may be carried out in vivo.
The term xe2x80x9cmanipulationxe2x80x9d in the context of the present invention refers to a change in at least one physiological property of said biological material. Typically, said manipulation is carried out in order to obtain a desired effect, as will be exemplified hereinbelow.
The term xe2x80x9cdesired effectxe2x80x9d refers to the final physiological property the method is intended to achieve and may refer to such properties such as enhanced metabolism, enhanced circulation or diffusion, improved ion cell membrane permeability, increased growth, proliferation, viability, improved healing, propagation, as well as the enhanced flow of fluids. The results may also be the disintegration of aggregates and the targeting of pharmaceutical substances, as will be explained below.
The term xe2x80x9ccoordinate varying magnetic fieldxe2x80x9d is a field that defines a magnetic field region (for a biological material to be located therein) and has a certain amplitude value of the wave of its magnetic induction, such that the amplitude value continuously displaces along the magnetic field region. The coordinate varying magnetic field (CVMF) is a field created by a system of magnetic poles that changes its position in time relative to the biological material located within the magnetic field region along at least one coordinate and in at least one direction. CVMF creates an electromagnetic disturbance and corresponding response inside the biological material in a plane inclined with respect to this at least one axis at a certain angle (e.g., right angle). This may, for example, lead to the creation of known magneto-hydro-dynamic effects. More specifically, if the biological material contains a liquid medium, CVMF can move the liquid medium inside the biological material in at least one direction along at least one coordinate. Another effect that can be achieved with the CVMF is the movement of a paramagnetic and ferromagnetic particle, as well as ions, in at least one direction along at least one coordinate. Additionally, the CVMF can cause the revolution of the particles. These effects are essentially different from those achieved with the pulsating fields that are characterized solely by time changes of their magnetic induction.
The term xe2x80x9csubjectingxe2x80x9d refers to the positioning of the biological material to be manipulated and a magnetic field source producing the CVMF with respect to each other, such that the biological material is located in or passes through the magnetic field region defined by the CVMF. This relative positioning should be such that an effective space xcex94 defined by the dimensions of the biological material and its distance from the magnetic field source is smaller than the half of a wavelength xcex of the wave of the CVMF. The wavelength xcex is defined by the accommodation of conductors of the magnetic field source.
By one aspect of the present invention, the manipulation of the biological material is achieved by directly subjecting the biological material to the magnetic field of the invention, without any need for the administration of any auxiliary substances.
It is known that all biological material contains electrolytes, which are effected to one degree or another by magnetic fields. Without wishing to be bound by theory, it is believed that by subjecting the biological material to a CVMF, at least one of the following physiological phenomena may take place:
1. The CVMF may enhance cytoplasmic flow inside cells. Said enhanced cytoplasmic flow inside cells may increase cellular metabolism, as well as improve the distribution of various nutrients, and intercellular factors within the cell. Said increase and said improvement may be utilized to improve proliferation, growth, viability, the propagation of differentiation of cells for cells present in an isolated cell culture, in tissues and tissue cultures, as well as in cells present in complex structures, such as organs kept in isolation, or inside the body.
For example, said improvement may be utilized to improve the growth of genetically engineered eukaryotic and prokaryotic cells grown in a bio-reactor, utilized for the production of desired biological material such as antibiotics, hormones, growth factors, and the like. It may improve growth rate, viability, and the proliferation of cells present in a tissue or in organs to be maintained for a prolonged period of time, or may increase the viability of the tissue or organ prior to implantation, for example, skin, cornea, kidneys, blood, bone marrow and the like. It may be used to improve the viability and proliferation of various organs and tissues present inside the body, for example to enhance healing processes of tissues such as cartilage, skin, bone, nerve muscle and the like.
Said enhancement may also be used to improve fertilization rate, if the magnetic field is applied to sperm, eggs or fertilized eggs kept in vitro, for example, for IVF purposes.
Where the method is used in connection with plants, it may be used to improve the rate of sprouting of plants from seeds, by increasing the viability and metabolism of each seed itself. In addition, it may be used to increase propagation from tissue culture, while at the same time decreasing the use of nutrients.
2. By another alternative, the CVMF may be used to improve or enhance the flow of electrolyte-containing liquids inside vessels such as blood or lymph vessels in animals, xylem or phlem vessels in plants, for example, to improve the transport of various beneficial substances, such as hormones, nutrients into vessels, or to enhance the clearance rate of various toxic substances through said vessels.
For example, the CVMF may be used in eukaryotic organisms to improve circulation, such as blood and lymph circulation through various blood and lymph vessels, especially in the periphery of the body. In the case of diabetes and other cases of obstructions of blood flow in small or large vessels, the coordinate-varying magnetic field may be used to improve said circulation. Another example is the improvement of blood flow to treat or alleviate impotence problems.
Another example is when the vessels are connected to various secretory glands, and application of coordinate-varying magnetic fields may be used to increase the secretion of various fluids from the glands and to improve their flow in the circulation. A specific example would be the mammary glands of lactating animals such as cows, sheep and goats, in which case the CVMF may be used to enhance and increase secretion of milk Another example is improvement of hormone secretion.
A specific example of the enhancement of flow, is the increase of flow in is plant xylem and phloem plantlets and plant cuttings which improve the provision of various nutrients to plant cells. The enhancement in connection with plants may also be the transport of various nutrients, the plant roots, or rootings.
3. By another alternative, a CVMF may be used to disintegrate various undesired aggregates present in biological material. The application of a CVMF to a biological material which contains electrolytes, which may also contain magnetic responsive material (such as for example iron present inside hemoglobin molecules) causes small vibrations at opposing directions of rotation and transportation, which may cause a disintegration of an aggregate.
By a specific example, where the aggregate is a blood clot, present inside a blood vessel, or an atherosclerotic clot present within a blood vessel, which partially, or completely blocks the blood vessel, the application of a CVMF may cause the integration of the aggregate into smaller particles which may be carried from the blocked site by the blood and cleared away.
Another aspect of the present invention is the manipulation of biological material by the objection to CVMFs, comprising also the administration of magnetic particles. The term xe2x80x9cmagnetic particlesxe2x80x9d refers to small units having magnetic properties, namely, those made of a ferromagnetic or paramagnetic material.
By one example, magnetic particles may be administered to the biological material, simply to enhance any of the above three physiological phenomena (enhancement of cytoplasmic flow, enhancement of flow inside vessels, and disintegration of particles) since the magnetic particles movement is effected by CVMF to a larger and more pronounced degree than the mere movement of electrolytes contained in biological liquids. However, by a preferred example, the lo magnetic particle may be (complexed, conjugated or coated) with a therapeutic agent, and the CVMF is used to target the complex (of magnetic particle-therapeutical agent) to a desired site in the biological material. Typically, this is a method carried out in vivo, wherein an individual is administered with said complexes, and then the CVMF is applied to the location where it is desired that the complex will concentrate, thus targeting the therapeutical material selectively to that region.
For example, the therapeutical agent may be an anti-cancer agent, such as cis platinum. The cis platinum is conjugated or complexed to magnetic particles, for example by coating magnetic particles with cis platinum.
The complexes are then administered to a subject having a localized cancer growth, for example, in a specific lymph-node, breast cancer, colon cancer, etc., and the CVMF is applied to the location of the tumor growth. Then, the conjugates of the magnetic particles/therapeutical substance which are present in the blood are directed by the CVMF towards a tumor growth site (due to the movement of the magnetic poles system created by the CVMF), so that their concentration at the desired site (being the tumor growth site) is much larger than the general concentration in the body, thus destroying the tumor in a selective manner.
There is thus provided according to one aspect of the present invention, a device for the manipulation of a biological material by a magnetic field, comprising a magnetic field source coupled to a current source for producing said magnetic field, the device being characterized in that:
the current source is of a kind supplying an electric current of at least two electrical degree shifted phases;
the magnetic field source comprises a two-part inductor, each inductor part producing a coordinate varying magnetic field (CVMF), wherein each inductor part is formed by at least two conductors aligned in a spaced-apart relationship, each of the at least two conductors being connectable to a different phase of the current source, each of the at least two conductors having two spaced-apart parts arranged such that when the conductor is connected to the current source, the electric current will flow in its two parts in opposite directions, respectively, the conductors being arranged such that each two locally adjacent conductor parts are associated with two different phases of the electric current source;
a distance between the two conductor parts coupled to the same phase of the current source defines a half-wavelength xcex/2 of a wave of magnetic induction of said CVMF, and is selected in accordance with a predetermined relation between the wavelength xcex and an effective space xcex94 within the magnetic field region defined by the dimensions of the biological material and its distance from the magnetic field source.
According to another aspect of the present invention, there is provided a method for the manipulation of a biological material to change at least one physiological property of the biological material to obtain a desired effect, the method comprising the steps of creating a magnetic field defining a magnetic field region for the biological material to be located therein, the method being characterized in:
(a) creating said magnetic field by creating a system of magnetic poles that changes its position in time along at least one coordinate and in at least one direction, said magnetic field being thereby a coordinate varying magnetic field (CVMF) that defines said magnetic field region and has an amplitude value of a wave of its magnetic induction continuously displaced along the magnetic field region in said at least one direction along said at least one coordinate, the magnitude of the magnetic induction being sufficient to cause said change of the at least one physiological property of the biological material;
(b) selecting the wavelength xcex of the wave of the magnetic induction and an effective space xcex1 within the magnetic field region, defined by the dimensions of the biological material and its location relative to the magnetic field source, in accordance with a predetermined condition of a relation between them; and
(c) locating the biological material within the magnetic field region for a time period sufficient for causing said change to obtain said desired effect.